Benjamin Wedro, MD, FACEP, FAAEM

Dr. Ben Wedro practices emergency medicine at Gundersen Clinic, a regional trauma center in La Crosse, Wisconsin. His background includes undergraduate and medical studies at the University of Alberta, a Family Practice internship at Queen's University in Kingston, Ontario and residency training in Emergency Medicine at the University of Oklahoma Health Sciences Center.

Melissa Conrad Stöppler, MD

Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.

Hemolytic uremic syndrome (HUS) facts

There are two types of HUS. Typical HUS follows a diarrheal infection often caused by E. coli OH157:H7. Atypical HUS is not associated with an infection of the digestive tract and has a less favorable outcome.

Symptoms of HUS include vomiting and diarrhea (often bloody), weakness, lethargy,
and bruising (purpura). These symptoms are due to a combination of dehydration,
anemia (due to the
destruction of red blood cells and low platelet counts), and uremia (the inability of the kidneys to clear waste products from the
body).

Diagnosis of HUS is made by a combination of history, physical exam, and abnormal
blood tests. There is no one test that makes the diagnosis of hemolytic uremic
syndrome.

Treatment of HUS is supportive with intravenous fluids. Anemia may require blood
transfusion and temporary dialysis may be necessary
to help treat kidney failure.

What is a "syndrome?"

In medicine, a syndrome is defined as a collection of symptoms (patient
complaints), signs (findings on physical examination), and laboratory or imaging
findings that tend to group together and be associated with a specific disease
or illness.

Shiga Toxin-Producing E. coli Infection Facts

Escherichia coli, or E. coli for short, is a very common bacterium. There are
hundreds of different strains of E. coli. Some are harmless while others cause
serious illness. Non-pathogenic strains of E. coli -- those that do not cause
disease -- are normal inhabitants of the intestinal tract in humans and animals.
But certain strains of E. coli can cause severe diarrhea and infect the genital
and urinary tracts.

What is hemolytic uremic syndrome (HUS)?

Hemolytic uremic syndrome (HUS) is a disease of two body systems, the blood
stream and the kidney. Hemolysis describes the destruction of red blood cells. In
hemolytic uremic syndrome, blood within capillaries, the smallest blood vessels in the body, begins to clot abnormally. When red blood cells pass through the clogged capillaries, they are sheared apart and broken. (hemo=blood +lysis=destruction). The second failed system, kidney failure (uremia), occurs when urea and other waste products build up in the bloodstream because the
kidneys cannot filter and dispose of them. (urea=a waste chemical + emia= in the blood).

HUS is also related to another disease caused by a similar normal clotting process
within the capillaries called thrombotic
thrombocytic purpura (TTP). Within the
medical literature, these two conditions are often considered together. HUS is
more widely known, however, because it has been discussed in the press because
of its relationship to a special type of
E. Coli (Escherichia coli) infection
associated with food poisoning.

HUS can be classified as typical or atypical. The typical type is associated
with gastrointestinal (GI) signs and symptoms including vomiting and diarrhea.
Atypical HUS is not associated with GI symptoms.

What causes hemolytic uremic syndrome?

While the cause of HUS has not been established with certainty, researchers
believe that an abnormal inflammatory reaction is stimulated in the blood stream
causing platelets (the parts of the blood that form clots) to sludge in small
blood vessels and form blood clots where they are not supposed to. This uses up
the platelets and causes a shortage of them in the rest of the body. This
abnormal reaction may be caused by a yet unidentified chemical that is produced
in blood plasma (the fluid or non-cellular part of the bloodstream).

The triggering events for HUS are varied and include:

Enterohemorrhagic E. Coli is a type of bacteria that causes
bloody diarrhea.
E. coli is a very common type of bacteria in the body, and it is only
the OH157:H7 type that causes the problem. It can be found in undercooked meat
and other foods; and is one of the causes of food recalls and restaurant-related
food poisoning outbreaks. This accounts for almost 90% of HUS in children. The
2011 outbreak of HUS in Germany was due to a different type of Shigela
toxin-producing E. coli called 0104:H4.

Pregnancy and the early postpartum (after delivery) time period and the use
of birth control pills are the more common associations with HUS.

Pneumonia caused by the
Streptococcus pneumoniae bacteria is another
possible precipitating factor. HUS is rare complication of this common
infection. Most often, this pneumonia is treated with antibiotics as an
outpatient. However, it is the cause of 40% of atypical HUS.

Medications may be also associated with HUS, including some chemotherapy
and immunosuppression drugs, birth control pills,
ticlopidine (Ticlid,
an anti-platelet drug) and
quinine (Quinerva,
Quinite) an anti-platelet drug.

AIDS may be associated with HUS.

Only the diarrheal form of HUS is considered to be typical HUS and is usually a disease of infants and children younger than 3 years of age.

The others are classified as atypical HUS and also include the familial form of the disease in which a gene mutation affects the blood clotting mechanism.

What are the signs and
symptoms of hemolytic uremic syndrome?

In typical HUS, gastroenteritis occurs with abdominal cramping,
vomiting and profuse bloody, watery diarrhea,
as a symptom up to a week before the onset of HUS. This may cause significant
dehydration, weakness and lethargy, as well as
electrolyte imbalances because of
the loss of sodium, potassium, and chloride in the
vomit and diarrhea. These symptoms
may resolve before the onset of anemia and the kidney failure symptoms of HUS.

The anemia and uremia usually present with weakness, lethargy, and
sleepiness. Seizures may occur. Purpura or small areas of bleeding in the skin may be seen because of
low platelet counts (thrombocytopenia).

How is hemolytic uremic syndrome diagnosed?

The health care professional will have a suspicion of the disease based on the
history and physical examination, especially in a small child who has had the
typical bloody diarrhea. Abnormal laboratory tests help confirm the
diagnosis. These abnormal findings may include:

Hemolytic anemia: the red blood cell count is low and a peripheral blood
smear, in which blood is examined under a microscope, will show that the red
cells have been damaged and destroyed. This differentiates hemolysis (hemo=blood
+ lysis=destruction) from anemia caused by decreased production of blood cells
in the bone marrow.

Uremia: Kidney function can be measured by testing the level of
waste products in the blood normally filtered by the kidney. BUN (blood urea
nitrogen) and creatinine are measures of this kidney function. When levels
rise, it is an indication of kidney failure or uremia in which the kidneys
cannot clear the waste products of metabolism from the body.

Abnormal urine findings: Blood and protein may be found in the urine when
normally they are not present.

Stool cultures: Since E. coli O157:O7 is the most common
cause of HUS in children; attempts are made to culture the bacteria from
stool samples.
The body usually clears the bacteria from the stool within a week, so a
negative test does not exclude the disease. A positive test helps confirm
HUS and will be reported to public health authorities to try to determine
the source of the infection. In 2011, outbreaks in Europe were traced by
public health authorities to tainted sprouts.

In atypical HUS, history is very important to search for other potential
causes of the disease. Unfortunately, the case may not be found in up to half of
cases of atypical HUS.

One of the distinguishing findings between HUS and TTP is a normal neurologic
examination. The brain function is normal in HUS.

What is the
treatment for hemolytic uremic syndrome?

Typical HUS in children tends to be self-limiting, and supportive care is often all
that is needed. This may include intravenous fluids for rehydration and
rebalancing of electrolytes like sodium and potassium, which can be lost with
the diarrhea.

Blood transfusions are only used for the most severe cases of anemia in which
the hemoglobin falls below 6 or 7 g/dL (depending on age, the normal value is
11-16).

Kidney failure
may be managed expectantly (by observation and supportive
care), and dialysis is not often required.

Adults with atypical HUS tend to become more ill and need more aggressive therapy than
children with the condition. In addition to the supportive care discussed above,
plasmapheresis or plasma exchange may be required. Since it is thought there is
an abnormal chemical in the plasma stimulating the abnormal clot formation,
removing the plasma and replacing it with donor plasma is helpful in treating
adult HUS.

Dialysis may be needed while awaiting recovery of the kidneys from
the illness.

Eculizumab (Soliris) has been approved by the FDA for the treatment of atypical HUS. It is a monoclonal antibody that decreases the blood clotting in the capillary blood vessels, decreasing the potential destruction of cells. This type of therapy decreases the body's immune capabilities, and the risk of infection increases.

What is the prognosis of hemolytic uremic syndrome?

Typical HUS in children tends to be self-limiting, and full recovery is most
likely.

Adults do less well. Without aggressive therapy like plasmapheresis and
dialysis, up to 25% of those affected with atypical HUS may die in the acute
phase of the disease, and 50% may have developed long-term kidney impairment.

Patients with HUS not related to a diarrheal illness have a worse prognosis
than those whose illness is due to gastrointestinal infection.

In those patients with genetically caused HUS, relapsing illness is common as
are kidney failure requiring dialysis and death.

How can hemolytic uremic syndrome be prevented?

Most cases of typical HUS associated with diarrhea can be prevented by thorough washing
and cooking of
food products. The vast majority of cases of typical HUS are caused by poor food
handling from the farmer to the wholesaler and grocer. Proper washing and
cooking techniques in the kitchen is the key to prevention.